Abstract
Abstract Recruitment of effector T lymphocytes into peripheral tissues, such as inflamed lung, contributes to an effective protection against infection and cancer. The rate of pathogen detection might be further influenced by the motility of recruited immune cells within three-dimensional tissues. Indeed, recent two-photon studies have shown that effector T cells navigate actively through inflamed lung tissue, but the molecular mechanisms that regulate this process are poorly characterized. Here, we used two-photon imaging of a murine lung treated with endotoxin to quantitatively analyze tissue navigation of lung-infiltrating CD8+ effector T cells. Tracking of individual T cells within inflamed lung tissue for several hours revealed that T cell movement transitions between periods of high directional persistence and confinement. Some T cells also moved in alignment with the vasculature. Treatment with pertussis toxin to inhibit chemokine receptor-dependent Gi-type G protein signaling led to a moderate reduction of the speed of lung-infiltrating T cells. Strikingly, pharmacological inhibition of the molecule ROCK, which promotes cytoskeleton-dependent squeezing through dense environments, led to a pronounced reduction of speed and almost completely abolished directional persistence of lung-infiltrating effector T cells. Together, these results show that migration of lung-infiltrating T cells is fine-tuned by environmental signals and dependent on the cell-intrinsic ROCK-signaling pathway.
Published Version
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